Recently, we demonstrated for the first time in human system the coexistence of tumor-specific cytotoxic and suppressor lymphocytes. Now, we plan to extend this preliminary observation to establish their clinical correlations, to probe in depth their interactions, and to distinguish tumor-specific cytotoxicity from natural cytotoxicity. Information thus obtained will facilitate our attempts to develop new immunotherapeutic modalities for malignant diseases. The clinical significance of cytotoxic and suppressor cells will be evaluated by a prospective study of patients' lymphocytes throughout their clinical courses. The mechanisms of interactions between cytotoxic and suppressor lymphocytes will be investigated by determining the tumor specificity of suppression, the possible involvement of soluble suppressive factor and the possible modulation of the interactions by thymic-humoral factor and various drugs. To differentiate tumor specific cytotoxicity from natural cytotoxicity, reactivities of lymphocyte against target cells of patient's tumor type, unrelated patient's tumor type and target cells susceptible to natural cytotoxicity will be compared with the reactivities of control lymphocytes against these target cells. Attempts will be made to separate the effector cells responsible for these two types of cytotoxicity and assess their roles in the immune surveillance of malignancies.